Enzyme sensitive, surface engineered nanoparticles for enhanced delivery of camptothecin.

Abstract

To achieve a drug delivery system combining the programmable long circulation and targeting ability, surface engineering nanoparticles (NPs), having a sandwich structure consisting of a long circulating outmost layer, a targeting middle layer and a hydrophobic innermost core were constructed by mixing a matrix metalloproteinase MMP2 and MMP9-sensitive copolymers (mPEG-Pep-PCL) and folate receptor targeted copolymers (FA-PEG-PCL). Their physiochemical traits including morphology, particle size, drug loading content, and in vitro release profiles were studied. In vitro studies validated that the inhibition efficiency of tumor cells was effectively correlated with NP concentrations. Furthermore, The PEG layer would detach from the NPs due to the up-regulated extracellular MMP2 and MMP9 in tumors, resulting in the exposure of folate to enhance the cellular internalization via folate receptor mediated endocytosis, which accelerated the release rate of CPT in vivo. The antitumor efficacy, tumor targeting ability and bio-distribution of the NPs were examined in a B16 melanoma cells xenograft mouse model. These NPs showed improved tumor target ability and enhanced aggregation of camptothecin (CPT) in tumor site and prominent suppression of tumor growth. Thus this mPEG-Pep-PCL@FA-PEG-PCL core-shell structure NP could be a better candidate for the tumor specific delivery of hydrophobic drug.

• Authors: Hongliang Yu, Jiao Chen, Sen Liu, Qian Lu, Jian He, Zhengyang Zhou, Yong Hu
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 216 Pg. 111-20 (Oct 28 2015) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 26282096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Polymers
• Polyethylene Glycols
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• Camptothecin

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacology)
• Camptothecin (administration & dosage, pharmacology)
• Cell Line, Tumor
• Drug Delivery Systems
• Endocytosis (drug effects)
• Humans
• Male
• Matrix Metalloproteinase 2 (biosynthesis)
• Matrix Metalloproteinase 9 (biosynthesis)
• Melanoma, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred ICR
• Nanoparticles (chemistry)
• Particle Size
• Polyethylene Glycols
• Polymers
• Surface Properties
• Tissue Distribution
• Up-Regulation (drug effects)
• Xenograft Model Antitumor Assays